Urban and industrial Superfund sites usually contain complex mixtures of contaminants, including aromatic hydrocarbons and heavy metals. The Hudson River has individual Superfund sites for PCBs, PCDD/Fs and Cr along with some of the highest sediment levels of PAHs of any estuary in the U.S. After decades of debate, the Hudson River PCBs Superfund site is designated for remediation beginning in the summer of 2009. In the late 1970s, Atlantic tomcod from the Hudson River exhibited one of the highest prevalences of tumors ever observed in a natural population concurrent with a dramatically truncated age structure. In a combination of field and laboratory studies, we propose to explore the prevalence of tumors and the age structure of the Hudson River tomcod population today, just prior to and during site remediation and the mechanistic basis of hepatic neoplasia and early life-stage toxicities in its population. In controlled laboratory studies, we propose to determine the sensitivity of young life-stages of tomcod to a suite of epigenetic alterations at the global and gene-specific levels resulting from exposures to Cr, benzo[a]pyrene, and perhaps PCBs. We will also compare the sensitivities of different individuals, ages, genders, and populations of tomcod to sensitive epigenetic changes. In parallel studies, the magnitude of these epigenetic changes will compared in tomcod from known contaminated sites in the Hudson River and from cleaner estuaries. Because the etiology of chemical toxicities, including hepatic neoplasia, probably involve a combination of genetic damage and altered gene expression, we will also explore the effect of co-exposure to Cr VI on sensitivity of tomcod to the generation of DNA adducts at the K-ras oncogene from B[a]P exposure. Our studies will complement those from other investigators in this program by evaluating the across taxa conservation of mechanisms of epigenetic and genetic toxicity and the applicability of their results to real-world in vivo environmental exposures of natural populations.